Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine

Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver.The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world.We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV.The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1.     

罗伊氏乳杆菌对轮状病毒感染肠炎患儿免疫功能与肠道菌群及临床疗效的影响

目的探究罗伊氏乳杆菌DSM 17938在治疗轮状病毒感染肠炎患儿中的疗效及对免疫功能、肠道菌群的影响。方法收集于2018年2月-2019年2月在阳光融和医院进行诊治的轮状病毒感染肠炎患儿126例,随机分为试验组(63例)和对照组(63例)。对照组给予常规补液治疗及蒙脱石散和枯草杆菌二联活菌口服治疗,试验组采用常规补液治疗及蒙脱石散和罗伊氏乳杆菌DSM 17938辅助治疗。观察两组患儿的腹泻改善情况,并分析对免疫功能(IgG、IgA、CD4^+/CD8^+水平)及肠道菌群失调的影响。结果在治疗72 h后,试验组患儿的治疗总有效率为92.06%,高于对照组的74.60%(P=0.009);且治疗后两组患儿的IgG、IgA、CD4^+/CD8^+水平均较治疗前有升高(P<0.05),且试验组水平高于对照组(P<0.05)。对患儿肠道菌群进行分析,在治疗1周后,试验组患儿肠道菌群失调程度低于对照组,且试验组的肠道菌群正常比例高于对照组(P<0.05)。结论罗伊氏乳杆菌DSM 17938对于辅助治疗轮状病毒感染肠炎患儿具有良好的疗效,能够提高患儿免疫力,改善肠道菌群失调,减轻患儿腹泻症状,具有一定的临床应用价值。     

The T2Bacteria Assay Is a Sensitive and Rapid Detector of Bacteremia That Can Be Initiated in the Emergency Department and Has Potential to Favorably Influence Subsequent Therapy

BackgroundBacteremia causes a major worldwide burden, in terms of financial and productivity costs, as well the morbidity and mortality it can ultimately cause. Proper treatment of bacteremia is a challenge because of the species-dependent response to antibiotics. The T2Bacteria Panel is a U.S. Food and Drug Administration–cleared and culture-independent assay for detection of bacteremia, including common ESKAPE pathogens—Escherichia coli, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa—and provides species identification in as little as 3.6 h directly from blood.ObjectiveOur aim was to evaluate the T2Bacteria assay performance and potential to affect patient care in the emergency department (ED).MethodsED patients from a Louisiana and Florida center were enrolled as part of the T2Bacteria Panel clinical study, which was prospective and noninterventional. Blood samples for blood culture (BC) and T2Bacteria were matched in time and anatomic location.ResultsData from 137 ED patients were evaluated. Relative to BC, T2Bacteria showed 100% positive percent agreement and 98.4% negative percent agreement. In addition, for species on the T2Bacteria Panel, the T2Bacteria assay detected 25% more positives associated with infection, and on average identified the infectious species 56.6 h faster. The T2Bacteria assay covered 70.5% of all species detected by BC. Finally, relative to actual care, the T2Bacteria assay could have potentially focused therapy in 8 patients, reduced time to a species-directed therapy in 4 patients, and reduced time to effective therapy in 4 patients.ConclusionsIn this ED population, the T2Bacteria assay was a rapid and sensitive detector of bacteremia from common ESKAPE pathogens and showed the theoretical potential to influence subsequent patient therapy, ranging from antibiotic de-escalation to faster time to effective therapy.     

马齿苋“成分-活性-中药功效-疾病”研究进展及关联分析

马齿苋是一种药食同源品,具有清热解毒、凉血止血、止痢的功效,为常见中药,作为药物安全性高。马齿苋具有多种活性成分及药理作用,为了充分开发利用马齿苋,加快马齿苋研究的现代化进程,综述马齿苋的研究进展并在此基础上对于其"成分-活性-中药功效-疾病"进行关联分析,为马齿苋的现代化研究提供思路。     

An Environmental Scan of the National and Provincial Diagnostic Reference Levels in Canada for Common Adult Computed Tomography Scans

Several regulatory bodies have agreed that low-dose radiation used in medical imaging is a weak carcinogen that follows a linear, non-threshold model of cancer risk. While avoiding radiation is the best course of action to mitigate risk, computed tomography (CT) scans are often critical for diagnosis. In addition to the as low as reasonably achievable principle, a more concrete method of dose reduction for common CT imaging exams is the use of a diagnostic reference level (DRL). This paper examines Canada's national DRL values from the recent CT survey and compares it to published provincial DRLs as well as the DRLs in the United Kingdom and the United States of America for the 3 most common CT exams: head, chest, and abdomen/pelvis. Canada compares well on the international scale, but it should consider using more electronic dose monitoring solutions to create a culture of dose optimization.     

基于UPLC-LTQ-Orbitrap-MS分析刺果番荔枝叶的化学成分

目的利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶的化学成分进行定性分析。方法采用Waters Acquity UPLC HSS T 3色谱柱(2.1 mm×100 mm,1.8μm),流动相为0.1%甲酸水(A)和乙腈(B)梯度洗脱,流速为0.3 mL/min,进样量2μL,在电喷雾正负离子模式下采集数据。经Reaxys数据库检索番荔枝属类化合物信息,通过质谱信息比对各化合物的m/z值、保留时间、质谱特征碎片等,并结合文献数据对鉴定的化合物进行验证。结果根据各化合物的特征裂解规律,从刺果番荔枝叶中共鉴定出45个化合物,包括16个生物碱类,14个番荔枝内酯类,7个黄酮类和8个其他类化合物,其中以番荔枝内酯类和生物碱类成分居多,与文献报道番荔枝内酯与生物碱类化合物是发挥抗癌的主要活性成分一致。结论利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶中的化学成分进行了快速、准确的定性分析,为刺果番荔枝叶的提取分离与药效物质基础的研究提供依据。